The DNA of a cell presents the first line of control over the metabolism and regulatory processes of the cell. The mechanisms by which the genetic message of the cell is maintained are of primary importance. The proposed research will utilize genetic and biochemical techniques to study the mechanisms of DNA replication. We will use bacterial mutants defective in replication for our studies. We will focus on the role of DNA polymerases in replication. Some E. coli temperature-resistant revertants appear capable of bypassing a defective DNA polymerase III and of using DNA polymerase I for replication. This argues that E. coli possesses alternate routes of DNA replication. The mutation which allows DNA polymerase I-dependent replication may be a recognized gene or it may not be. It must be located by mapping. The biochemistry of replication in the TR revertants will be explored in lysate systems using phage DNA for replication. We will investigate the specific properties of the DNA polymerase involved in replication. In some instances, this appears to be the result of an unusual suppressor mutation. Particular attention will be paid to the control of DNA replication, particularly the initiation process and possible alterations in the revertants as a basis for alternate mechanisms of replication. The existence of mutants altered in DNA replication properties promises better understanding of the replication pathway.